Purpose: To evaluate 2 different applications of an intra-articular (IA) mixture composed of 40 mL 0.25% bupivacaine and 2 mg morphine in anterior cruciate ligament (ACL) reconstructions, before and after tourniquet release. Type of Study: Prospective, double-blind, randomized, clinical trial. Methods: Forty patients who underwent ACL reconstruction were prospectively randomized into 2 groups. Group 1 was injected with IA morphine with bupivacaine 10 minutes before tourniquet release. Group 2 was injected with IA morphine with bupivacaine injection after tourniquet release, after a 30-minute period of waiting with closed drainage. Visual analog scale scores were recorded at 10 and 30 minutes and at 1, 2, 4, 8, 12, and 24 hours after surgery. Detailed records were kept of the amount of analgesic drug required. Results: In pain scores, there was no difference between the 2 groups except for 30 minutes postoperatively (P = .005). The first analgesic requirement time was significantly lower in group 2 (P < .001) and the total amount of opioid used was lower in group 2 (P = .037) than those in group 1. There was no difference between the 2 groups in terms of operation time (P = .484), although there was a significant difference between groups in terms of tourniquet time (P = .024). Conclusions: We conclude that IA analgesic injection after tourniquet release is more beneficial to obtain postoperative analgesia in ACL reconstructions than the same injection before tourniquet release. Level of Evidence: Level I.